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SP0142 Cell Migration in Rheumatoid Arthritis
  1. M. Connolly1
  1. 1Rheumatology, Conway Institute of Biomedical and Biomolecular Research and St. Vincent’s University Hospital, UCD, Dublin, Ireland

Abstract

Rheumatoid arthritis (RA) is a progressive autoimmune disease. An early event in inflammation is angiogenesis where new blood vessels invade synovial tissue facilitating a self-perpetuating infiltration of immune cells. This results in lining layer hyperplasia and the destruction of adjacent articular cartilage. Cell migration and altered vascular morphology are fundamental processes in RA synovial tissue infiltration and invasion. Leukocyte extravasation occurs through a multistep process, involving first the selectins, then chemoattractant receptor signaling, followed by firm adhesion to vessel walls through the actions of integrins. When activated immune cells migrate, they become polarised forming membrane protrusions at the leading edge. This process depends on integrin–focal adhesion kinase (FAK) signalling pathways and is accompanied by the recruitment of cytoskeletal proteins which regulate cytoskeletal assembly/disassembly. Engagement of integrin receptors results in the downstream activation of ρ-family GTPase proteins, Rac-1, RhoA and Cdc42, involved in actin/stress fibre maintenance and turnover, stimulating cell contraction, which allows cell body movement to form filopodia, lamellipodia and membrane ruffling. In addition to immune cells, activated RA synovial fibroblasts, present in large numbers in rheumatoid synovium, play a critical role in the destructive process of RA. RASFs mediate disease progression by attaching to, invading into and degrading adjacent cartilage and bone by producing matrix-degrading enzymes after upregulating adhesion molecules. Current ongoing clinical trials will provide considerable new insight into cell migration as a therapeutic target in inflammatory arthritis.

Disclosure of Interest None Declared

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